The goal of the present application is to elucidate basic molecular mechanisms responsible for cell cycle progression in B cells, by studying the competence/progression model in which the later steps of cell cycle progression induced by the actin active drug, cytochalasin, are separable from the early steps of activation (or competence induction) induced by anti-Ig. This will be pursued by analyzing several specific intracellular changes produced by cytochalasin that are potentially implicated in signal transduction, and by evaluating the mechanisms responsible for cytochalasin induced changes in gene expression, including the cytochalasin induced increase in c-myc transcription. The following approaches will be undertaken to address these issues: 1) Phosphoinositide based signaling events triggered by cytochalasin will be studied to determine whether G proteins are involved in the coupling of actin to PL-C (using GTP analogues), whether increased intracellular Ca++ results from phosphoinositide turnover (using a fluorescent, Ca++ sensitive dye), and whether PK-C is activated (as judged by phosphorylation of added histone or endogenous proteins). 2) Dynamic changes in the association of actin binding proteins (ABP) to actin as a result of cytochalasin treatment will be evaluated (by isolating ABP in association with actin on a DNase column and visualizing proteins by 2 dimensional gel electrophoresis). 3) The cytoplasmic signals responsible for the induction of c-myc mRNA by cytochalasin will be evaluated using metabolic inhibitors (in conjunction with Northern blot analysis). 4) The mechanisms of c-myc gene transcriptional induction stimulated by cytochalasin will be evaluated (by gel retardation assay and DNase hyper-sensitivity). 5) The induction of new mRNA transcripts will be determined (by differential hybridization analysis). Elucidation of the mechanisms responsible for cell cycle progression in B cells will increase understanding of the proliferation that characterizes clonal expansion. this may suggest means of influencing B cell dyscrasias associated with abnormal or excessive clonal expansion, such as autoimmune states neoplastic lymphomas.